Elevated fasting glucagon is linked to hyperglycemia, but postprandial glucagon effects are less understood. Recent evidence suggests metabolic benefits of rising glucagon after oral glucose intake, potentially impacting brain-mediated whole-body metabolism. To elucidate the translational relevance of these findings, we studied postprandial effects of glucagon on the human brain. We performed oral glucose tolerance tests (OGTT) combined with functional magnetic resonance imaging to quantify brain activity and connectivity at fasting, 30 and 120 min post glucose load in 30 volunteers. In 14 participants with suppressed glucagon, low-dose glucagon infusion mimicked non-suppressed glucagon after OGTT. This was compared to 7 participants with endogenous rising glucagon during OGTT. Low-dose glucagon infusion did not elevate plasma glucose levels during OGTT. Also, no changes in insulin sensitivity and insulin secretion were observed. However, experimentally elevating glucagon during OGTT in individuals with physiological suppression of glucagon significantly increased postprandial brain responsivity in the hippocampal gyrus and in brain regions important for the homeostatic and hedonic regulation of food intake as well as systemic metabolism (i.e., hypothalamus and ventral striatum). Most postprandial brain responsiveness during glucagon infusion was directionally consistent with the findings in persons with endogenously rising glucagon. Moreover, the postprandial brain response correlated with the rise in glucagon, regardless of exogenous or endogenous source of glucagon. Although the overall glucagon trajectory during OGTT was not significantly different over the full 0-150 min period, the groups differed at key post-challenge timepoints and in integrated glucagon exposure. Together with the infusion and correlation analyses, this supports a relationship between postprandial glucagon and brain responsivity, while more subtle differences in glucagon kinetics will require larger studies. Our findings demonstrate postprandial effects of glucagon in metabolically relevant human brain areas. This may underlie the promising effects on body weight achieved with pharmacological multi-agonists that activate the glucagon receptor.
Resistance to thyroid hormone (RTH) is a rare endocrine disorder, most commonly caused by mutations in the thyroid hormone receptor β (TRβ) gene, resulting in the RTH beta (RTHβ) subtype. In contrast, autoimmune thyroid disease (AITD) is common. The coexistence of RTHβ with AITD has not been fully clarified. Here, we describe a family in which RTHβ coexists with AITD, highlighting the complex interplay between these disorders. A 45-year-old woman, previously for years treated for hyperthyroidism, presented after a decade-long gap in follow-up, reporting palpitations and fatigue. Laboratory evaluation revealed elevated free thyroxine (fT4 34 pmol/L) and free triiodothyronine (fT3 11.8 pmol/L) with inappropriately normal thyroid-stimulating hormone (TSH 1.87 µIU/mL). Thyroid antibodies, anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) were positive, while TSH receptor antibodies (TRAb) was negative. Thyroid ultrasound demonstrated a mildly enlarged gland with clinically insignificant nodules, and Tc-99 m scintigraphy showed normally functioning tissue. Pituitary MRI was normal. The thyrotropin-releasing hormone (TRH) stimulation test demonstrated an exaggerated TSH response, consistent with RTHβ. Genetic testing confirmed a heterozygous pathogenic thyroid hormone receptor β THRB variant. Further evaluation of the patient’s family and genetic testing confirmed RTHβ in her daughter and sister, both of whom also had coexisting AITD. The clinical phenotype of RTHβ is highly variable, ranging from asymptomatic individuals to features of hypo- or hyperthyroidism. Variable tissue responsiveness underlies the overlapping features of thyroid hormone excess and deficiency seen in RTHβ. Coexisting primary hypothyroidism due to AITD can further complicate the clinical course, creating diagnostic and therapeutic challenges. This overlap presents unique challenges in diagnosis and management, often leading to diagnostic uncertainty and therapeutic difficulties. Management should be patient-centred, emphasising individual assessment, multidisciplinary collaboration, and long-term follow-up to optimise outcomes and quality of life.
Depressive symptoms during pregnancy are linked to adverse offspring outcomes, but the underlying biological mechanisms remain unclear. Evidence suggests that maternal stress may alter placental biology and function. We, therefore, examined whether placental telomere length (TL) and mitochondrial DNA alterations, including copy number and heteroplasmic burden, could be associated with antenatal depressive symptoms (ADS). Placental samples (n = 107) from the STRiDE pregnancy cohort were collected at birth. Participants were classified as ADS (n = 54) and controls (n = 53) based on PHQ-9 scores at 24-28 gestational weeks. Placental TL and mtDNA copy number (mtDNA-CN) were measured by qRT-PCR, and mitochondrial genome sequencing was performed using next generation sequencing. Placental TL (Median: 0.430 vs 0.440; p = 0.006) and mtDNA-CN (Median: 0.715 vs 0.990; p = 0.005) were significantly reduced in the ADS group compared to controls. Linear regression analyses showed that higher PHQ-9 scores were significantly associated with shorter placental TL (β = -0.012, p < 0.001) and lower placental mtDNA-CN (β = -0.072, p < 0.001) after adjusting for potential confounders. Mitochondrial genome analysis revealed a higher heteroplasmic burden, including four novel heteroplasmic variants and one deleterious mutation (m.7458G > A in MT-TS1) in ADS. In conclusion, lower placental TL and mtDNA-CN were associated with ADS, suggesting impaired mitochondrial and telomeric integrity. A higher heteroplasmic burden and the presence of a potentially deleterious variant in ADS suggest that mitochondrial genome instability could be mediated by ADS.
SOX3 is a single-exon gene located on the X chromosome (Xq27.1), encoding a transcription factor critical for early central nervous system and pituitary development, as well as gonadal function. A growing body of literature reports a diverse array of phenotypes associated with different classes of SOX3 variants, including single nucleotide variants, indels, polyalanine tract changes, copy number variants, and structural rearrangements. These variants have been implicated in conditions ranging from pan-hypopituitarism or isolated growth hormone deficiency to neural tube defects, disorders/differences in sex development, and complex syndromes involving craniofacial and intellectual disability. In this review, we comprehensively summarize all known variants involving SOX3 reported to date, highlighting the different pathogenetic mechanisms that have been reported or hypothesized (e.g., gene dosage, transcriptional regulation) and the phenotypes to which these variants are associated to. Special emphasis is placed on established genotype-phenotype correlations and the challenges in interpretation relevant to clinical diagnostics. This review aims to provide a reference framework for clinicians, researchers, and geneticists working with SOX3-related disorders.
Malnutrition and frailty are prevalent issues in nursing homes, leading to increased dependence and morbidity. N-3 polyunsaturated fatty acids (PUFAs), i.e. linolenic, eicosapentaenoic, and docosahexaenoic acids, have demonstrated potential benefits in mitigating inflammation, cognitive decline, and sarcopenia. However, there is limited evidence on the impact of dietary n-3 PUFAs enrichment in preventing independence loss in the older patients and particularly nursing home (NH) residents. The trial aims to evaluate whether an n-3 PUFAs-enriched diet to cover the recommended daily allowance needs can slow down the decline in independence among older residents in NH. A prospective, randomized, controlled, open-label, multicenter trial will be conducted in NH. The study population (n=432) will be cluster-randomized into two groups: 1- an intervention group receiving an n-3 PUFAs enriched diet, and 2- a control group receiving the usual institutional diet. The primary outcome will be the change in independence, measured by the Activities of Daily Living-Long Form Score (ADL-LFS) at 24 months. Secondary outcomes will include ADL-LFS at 6, 12, and 18 months, nutritional status, body composition, muscle function, fall incidence, infection rates, cognitive function, depression scale, n-3 and n-6 PUFAs blood levels, and healthcare resource utilization. In a subgroup of patients (n=30 per group), data on actimetry will be collected. Statistical analyses will be conducted using a generalized linear mixed model to account for clustering effects. This trial will assess whether an n-3 PUFAs enriched diet has the potential to slow the loss of independence in NH residents. The findings could have potential implications for nutritional policies in NH and clinical guidelines. NCT05628155 (clinicaltrials.gov). CPP Île de France X, on January 12, 2023, under the number #2022-A00850-43.
Autosomal dominant acute porphyrias are rare inherited disorders of haem biosynthesis characterised by accumulation of potentially neurotoxic porphyrin precursors and attacks of severe abdominal pain with autonomic and neuropsychiatric features. Disease severity ranges from asymptomatic individuals to those with recurrent, life-threatening attacks. The International Porphyria Network invited 34 acute porphyria specialists from 17 countries to form an expert panel. The invited group included clinicians from diverse specialities (ie, internal medicine, haematology, endocrinology, gastroenterology, hepatology, neurology, and biochemistry), together with laboratory scientists and patient representatives. The panel met online (in 2023-25) to develop 15 evidence-based recommendations with the use of the Grading of Recommendations, Assessment, Development, and Evaluations framework addressing attack prevention, management of sporadic and recurrent attacks, long-term follow-up, surveillance for primary liver cancer, and family screening. The guidelines support safe, consistent clinical care and improved outcomes, recognising global variation in resources and access to high-cost drugs, and highlighting priorities for future research.
Obesity-associated metabolic dysfunction-associated steatotic liver disease (MASLD) and its progression to steatohepatitis (MASH) with advanced fibrosis pose a major global health challenge. Targeting γ-aminobutyric acid (GABA)ergic system has shown promise in mitigating liver injury. Therefore, we investigated HK3, a positive allosteric modulator of the GABAA receptor, as a potential therapy for MASH, with a particular focus on liver fibrosis and obesity. Human-derived 3D MASH spheroids (n = 4-27) and hepatic stellate cells (LX2, n = 3-5) were treated with increasing concentrations of HK3 or its derivative HK1 to assess their anti-steatotic, anti-inflammatory and anti-fibrotic efficacy. Molecular and transcriptional responses were assessed by immunoblotting, ELISA, reverse-transcription PCR and RNA sequencing. The in vivo effects of HK3 (10 or 25 mg/kg) were evaluated in carbon tetrachloride-induced fibrosis (n = 10) or diet-induced obesity (n = 6-7) mouse models. Adipocytes (3T3-L1, n = 5-8) and visceral adipose tissue from C57BL/6 mice (n = 6) were treated with HK3 or HK1 to determine their impact on mitochondrial respiratory function by extracellular flux analysis and high-resolution respirometry. The most effective concentration of HK3 reduced intracellular lipid content, interleukin secretion and pro-collagen 1αI levels (p <0.0001, p <0.05, p <0.01) in the organotypic 3D human MASH model. In hepatic stellate cells, HK3 and HK1 dose-dependently attenuated TGF-β1-induced fibrotic and inflammatory biomarker expression (p <0.0001) and diminished cell migration (p <0.0001). In vivo, HK3 prevented fibrosis progression (p <0.05) in a carbon tetrachloride mouse model and reduced body fat mass (p <0.0001) in a diet-induced obesity mouse model. Accordingly, HK3 increased proton leakage and mitochondrial uncoupling efficiency in adipocytes (p <0.0001) and visceral adipose tissue (p <0.001). HK3 attenuates hepatic fibrosis in preclinical MASH models, while reducing body fat through adipocyte mitochondrial uncoupling. Thus, HK3 offers a promising multi-targeted first-in-class pharmacological approach for obesity-associated MASLD. Obesity-related fatty liver disease can progress to severe liver scarring, yet effective treatments targeting both liver damage and metabolic dysfunction remain rare. This study investigates HK3, a novel small molecule, which reduced liver fat, inflammation, and scarring while also lowering body fat in multiple preclinical models. These findings are particularly relevant for patients with obesity-related fatty liver disease, where current therapies often fail to adequately address fibrosis, the main driver of disease progression. If confirmed in clinical studies, HK3 could support the development of multi-target treatments that simultaneously improve liver health and metabolic balance.
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The ISCHIA study demonstrated that intermittently scanned continuous glucose monitoring (isCGM) combined with structured education effectively reduced the time below range (TBR) in individuals with type 1 diabetes. Given that the influence of sex on CGM metrics has remained unclear, we performed a post hoc analysis of the ISCHIA study to evaluate the impact of isCGM together with structured education on TBR and other parameters in men and women separately. Data for 93 individuals who completed the ISCHIA study were analyzed. Baseline characteristics and intervention outcomes, including CGM indices and quality of life (QOL) scores, were stratified by sex for comparative analysis. Age, body mass index, disease duration, and insulin dosage at baseline did not differ significantly between men and women. Intervention outcomes including TBR (9.9±6.2% vs 10.3±7.6% for men vs women, respectively), time in range (61.5±11.2% vs 59.7±10.9%), and time above range (28.6±12.7% vs 30.0±13.4%) as well as QOL scores also did not show any significant sex differences. The use of isCGM together with structured education was suggested to be effective in reducing TBR among individuals with type 1 diabetes regardless of sex. J. Med. Invest. 73 : 74-79, February, 2026.
Capivasertib, an AKT (protein kinase B) inhibitor, in combination with fulvestrant, reduces the risk of progression in recurrent breast cancer; however, it frequently leads to hyperglycemia by disrupting the insulin signaling pathways. Insulin-based therapies are generally ineffective in this setting and may worsen cancer outcomes. Herein, we report a case of capivasertib-induced diabetes successfully managed with insulin-independent glucose-lowering agents while capivasertib therapy was continued. A 57-year-old female with a body mass index of 23.0 kg/m² developed hyperglycemia one month after initiating capivasertib, with a glycosylated hemoglobin (HbA1c) level of 7.3%. A 75-g oral glucose tolerance test (OGTT) confirmed the diagnosis of diabetes according to the American Diabetes Association diagnostic criteria, demonstrating a fasting glucose level of 173 mg/dL, a two-hour glucose level of 512 mg/dL, and marked hyperinsulinemia. The markedly elevated glucose levels observed during the OGTT likely reflect severe drug-induced hyperglycemia associated with AKT inhibition, rather than a typical OGTT response in untreated diabetes. Treatment with empagliflozin (10 mg/day, a sodium-glucose cotransporter-2 inhibitor) and voglibose (0.4 mg/day, an alpha-glucosidase inhibitor) improved the HbA1c level to 6.3% within two months. After five months, a repeat OGTT showed improvement, shifting from the level of diabetes to impaired glucose tolerance, with substantially reduced insulin levels. This case may represent one of the early reports describing the successful management of capivasertib-induced diabetes with insulin-independent glucose-lowering agents, suggesting a potential strategy for managing AKT inhibitor-induced hyperglycemia.
Burosumab is effective for treatment of rickets in children with X-linked hypophosphatemia (XLH). The effects of burosumab on markers and regulators of osteoblast and osteoclast acitivity are largely unknown. In this cross-sectional observational study, we investigated 7 key markers and regulators of osteoblast and osteoclast activity in 107 burosumab-treated children with XLH. We calculated z-scores for bone-specific alkaline phosphatase (BAP), procollagen-1-N-terminal propeptide (P1NP), carboxy-terminal telopeptide of type 1 collagen (CTX), tartrate-resistant acid phosphatase type 5b (TRAP5b), soluble receptor activator of NF-κB ligand (sRANKL), osteoprotegerin (OPG), and sclerostin. The median age at investigation and duration of burosumab treatment were 10.7 and 2.2 yr, respectively, with 18.7% of patients on primary burosumab treatment and 81.3% with prior treatment with phosphate and active vitamin D. Height and body mass index improved by approx. 0.3 z-score from baseline with burosumab treatment, and serum phosphate, 1,25-dihydroxyvitamin D, and alkaline phosphatase improved by 2 z-scores (each p < .01 versus prior burosunab), but phosphate (-1.8 z-score) and calcium (-0.65 z-score) remained reduced (each p < .001 versus age and sex specific reference values). The z-scores for osteoblast (BAP, P1NP) and osteoclast (CTX, TRAP5b) activity markers and for the osteoblast suppressor sclerostin were increased (each p < .001). Standardized sRANKL was reduced (p < .05), while the RANKL inhibitor OPG was increased resulting in a reduced sRANKL/OPG ratio (each p < .001). Multivariate analysis revealed significant associations between serum sclerostin and serum phosphate (negative), serum calcium and vitamin D sufficiency (positive), and primary burosumab treatment with BAP (negative). In this real-world setting, pediatric XLH patients receiving burosumab treatment showed persisting mild hypophosphatemia and increased markers of osteoblast and osteoclast acitivity despite negative counter-regulation of osteoblasts by sclerostin and osteoclasts by OPG/RANKL. Our data suggest a more pronounced normalization osteoblast activity when children are primarily treated with burosumab and underscore the need for adequate vitamin D supplementation. Burosumab is effective in healing of rickets in children with X-linked hypophosphatemia. Its effects on osteoblast and osteoclast acitivity are largely unknown. We investigated markers and regulators of osteoblast and osteoclast activity in 107 pediatric XLH patients treated with burosumab for 2.2 yr. Height, BMI, phosphate and alkaline phosphatase improved with burosumab, but patients showed persisting mild hypophosphatemia and increased markers of osteoblast and osteoclast acitivity despite negative counter-regulation of osteoblasts by sclerostin and osteoclasts by OPG/RANKL. Our data indicate better normalization of osteoblast activity when children were primarily treated with burosumab and underscore the need for vitamin D supplementation.
Background and Clinical Significance: Neurosarcoidosis (NS) is a rare manifestation of systemic sarcoidosis involving the central nervous system, with highly variable neurological and endocrine presentations. Among these, anterior pituitary dysfunction is particularly uncommon and diagnostically challenging. Case Presentation: We report the case of a 37-year-old woman with a 4-year history of secondary amenorrhoea and an initially suspected pituitary microadenoma, who was ultimately diagnosed with probable NS presenting with multiaxial anterior pituitary insufficiency. Early magnetic resonance imaging (MRI) revealed a small pituitary lesion and isolated pituitary stalk thickening, without other central nervous system abnormalities. Subsequent imaging demonstrated contrast-enhancing lesions involving the meninges and cranial nerves, along with progression of pituitary stalk involvement and loss of the posterior pituitary bright spot. Further evaluation confirmed systemic sarcoidosis. High-dose corticosteroid therapy led to partial clinical and radiological improvement; however, relapse necessitated methotrexate, and persistent pituitary hormone deficiencies required long-term hormonal replacement. Conclusions: This case highlights the diagnostic complexity of NS presenting with isolated endocrine dysfunction and subtle imaging findings. It underscores the need to consider systemic sarcoidosis in patients with unexplained hypopituitarism.
Osteoarthritis patients undergoing THA or TKA were studied to compare the cumulative incidence of revision after perioperative denosumab versus alendronate. Denosumab was not associated with differences in the incidence of revision after THA but was associated with a higher revision incidence after TKA, mainly driven by aseptic tibial loosening. Osteoarthritis is highly prevalent, and the number of total hip (THA) and knee arthroplasties (TKA) continues to rise. This study aimed to evaluate the risk of revision associated with perioperative exposure to denosumab versus alendronate in patients undergoing THA or TKA for osteoarthritis. This retrospective cohort study used data from the Emilia-Romagna Registry of Orthopedic Prosthetic Implants (RIPO). Patients undergoing primary THA or TKA for osteoarthritis between 2011 and 2023 were included. Perioperative exposure was defined as at least one dispensing of denosumab or alendronate within 180 days before or after surgery. The primary outcome was first revision. Revision risk was analysed using cumulative incidence functions, treating death and emigration as competing events, and groups were compared using Gray's test. The THA cohort comprised 129 denosumab and 922 alendronate users. Revision occurred in 4 denosumab (3.1%) and 21 alendronate patients (2.3%); no significant difference was observed in competing risk analyses (Gray's p = 0.623). In the TKA cohort, 117 denosumab and 940 alendronate users were analysed. Here 8 denosumab patients (6.8%) and 18 alendronate patients (1.9%) required revision, with a significant difference in cumulative incidence (Gray's p = 0.002). Revisions in denosumab users were mainly due to aseptic tibial loosening. Perioperative denosumab exposure was associated with a higher cumulative incidence of revision after TKA in this cohort. These findings should be interpreted cautiously and do not imply causality. The observed pattern may reflect complex interactions between antiresorptive therapy and joint-specific biomechanical factors, which warrant further investigation.
Obstructive sleep apnea is a common yet under-recognized condition. 80% of sleep apnea cases go undiagnosed, and it is a common contributor to sudden death. Therefore, a simple and sensitive screening tool is the need of the hour. We developed a simple, more convenient, and user-friendly 3-question screening tool to identify individuals at risk of obstructive sleep apnea.
The fibrosis-4 (FIB-4) score is used to identify risk of advanced liver fibrosis. This post hoc analysis investigated its prognostic value for cardiovascular (CV) outcomes and its relevance to the effects of dapagliflozin. DECLARE-TIMI 58 was a randomised, placebo-controlled phase 3 trial investigating dapagliflozin in patients with type 2 diabetes (T2D) and either atherosclerotic cardiovascular disease (ASCVD) or high ASCVD risk. Participants were stratified by baseline FIB-4 scores (< 1.30, 1.30 to < 2.67, and ≥ 2.67). Hazard ratios (HRs) and 95% confidence intervals (CIs) for dapagliflozin versus placebo were calculated for the two primary outcomes (major adverse cardiovascular events [MACE] and the composite of CV death and hospitalisation for heart failure [HHF]). Of 17 160 patients enrolled, 16 361 were included (median follow-up of 4.2 years). Distribution across FIB-4 categories was: < 1.30, n = 9084 (55.5%); 1.30 to < 2.67, n = 6556 (40.7%); and ≥ 2.67, n = 621 (3.8%), with similar ASCVD prevalence across groups (40%-43%). In the placebo arm, the ≥ 2.67 FIB-4 group had the highest event rates for MACE, HHF, CV death, and all-cause death. MACE HRs (95% CIs) for dapagliflozin versus placebo were 0.95 (0.83-1.10), 0.92 (0.79-1.08), and 0.61 (0.38-0.97) across ascending FIB-4 groups. For the CV death and HHF composite endpoint, they were 0.81 (0.67-0.98), 0.90 (0.73-1.10), and 0.50 (0.28-0.90). Dapagliflozin reduced aspartate aminotransferase and alanine aminotransferase levels compared with placebo. Highest FIB-4 scores were associated with increased CV risk in patients with T2D. Dapagliflozin reduced CV risk across FIB-4 categories without significant interactions.
Severe, early-onset obesity is a monogenic disorder in a subset of patients. Recently, rare protein-truncating variants (PTVs) in BSN and APBA1 have been implicated as monogenic causes of obesity. Truncating variants in these two genes have been associated with adult-onset monogenic obesity. Here, we aimed to investigate the occurrence of rare PTVs in APBA1 and BSN in minors with severe obesity manifesting in early childhood or adolescence. Previously obtained exome data of 209 children and adolescents (0–18 years) with severe obesity manifesting in early childhood or adolescence genetically tested at the Ulm University Medical Center between April 2022 and May 2024 were mined for rare PTVs in APBA1 (NM_ 001163.4; NP_ NP_001154.2) and BSN (NM_003458.4; NP_003449.2). In all patients, monoallelic, and in the case of autosomal-recessive inheritance, biallelic likely pathogenic and pathogenic variants in well-known obesity-associated genes were excluded. Clinical re-evaluation was performed in two identified cases with rare potentially protein-truncating variants in APBA1. The first patient (male, 15 years) presented with a BMI of 33.7 kg/m2 (BMI z-score: 2.7) after nine years of excessive weight gain despite life-style interventions. He had a body fat percentage of 49.5% and showed hyperphagia. The patient displayed impaired expressive language development, dyslexia and an IQ of 84. His mother also had obesity and dyslexia while his father and younger sister were unaffected. We identified the heterozygous, likely pathogenic variant APBA1:c.814C > T;p.(Gln272*) in the index patient and his mother. The second patient (male, 6 years) presented with a BMI of 30.0 kg/m2 (BMI z-score: 3.8), a body fat percentage of 43.6% and hyperphagia. The child had upslanting palpebral fissures and showed impaired expressive language development. Both parents of the boy were affected by severe obesity and underwent bariatric surgery. We identified the heterozygous variant of unknown significance APBA1:c.2442 + 3A > C predicted to impair proper splicing in the index patient and his mother. We conclude that rare potentially protein-truncating variants in APBA1 are also found in some minors with early-onset and severe obesity. Therefore, those variants might not be restricted to adult-onset disease. We therefore propose to include APBA1 in diagnostic genetic testing for monogenic obesity in minors and adults.
In heart failure (HF), patients' quality of life (QoL) is influenced not only by cardiac function but also by coexisting conditions. Despite the widespread use of QoL assessments, the role of patient-related factors as determinants of QoL remains not fully elucidated. This study aims to assess the relative impact of different factors on QoL in HF patients, also its impact on mortality in this group. The study was based on the national registry - HEart failuRe ObsErvational Study of the Polish Cardiac Society, where QoL was assessed at baseline (Kansas City Cardiomyopathy Questionnaire [KCCQ]-12), and follow-up data on all-cause mortality were obtained. Adjusted linear regression was used to identify factors associated with KCCQ-12. The study included 1397 patients with a mean KCCQ-12 score = 47.92 (28.65-72.92). Higher New York Heart Association class had consistently significantly lower values of all KCCQ-12 domains and KCCQ-12 overall score (85 [69-93] vs. 65 [46-79] vs. 35 [23-49] vs. 21 [10-38]; all P <0.001). Hospitalized patients had significantly lower KCCQ-12 overall score, with a significant difference between patients hospitalized for HF or non-cardiac reasons and patients hospitalized for other cardiac conditions. Apart from visit type, individual factors, cardiovascular conditions, and non-cardiac conditions were independently associated with KCCQ-12. KCCQ-12 also significantly influenced all-cause mortality (hazard ratio per 1 point increase = 0.976; 95% confidence interval, 0.970-0.981; P <0.001). Individual factors with both cardiac and non-cardiac comorbidities are independently associated with QoL in patients with HF. The KCCQ-12 integrates all of these factors and may serve as a simple, easily accessible tool for prognostic assessment.
Glucocorticosteroids (GCs) are commonly used in the treatment of autoimmune, inflammatory and neoplastic diseases. Although clinically effective, they are associated with significant metabolic side effects, including increased insulin resistance, impaired function of pancreatic β-cells, and, finally, weight gain. These effects can result in steroid-induced hyperglycemia (SIH) and steroid-induced diabetes (SID), both of which increase the risk of complications such as infections and prolonged hospitalisation. Intensive insulin therapy remains the standard treatment for SID. However, emerging evidence suggests that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) may have therapeutic potential to counteract the metabolic effects of steroids. This review evaluates the efficacy and safety of GLP-1 RAs for the treatment of SIH and SID.
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